To reduce health disparities, national targets were set in Healthy People 2010 to increase the rates of initiation and duration of breast feeding. Although initiation rates are nearly met, the targets set to sustain breastfeeding are far from being met. Mother's with lower incomes and educational levels whose infants are at greatest risk of poor health were more likely to stop breastfeeding early. Early cessation of breastfeeding has psychological, social and physiological causes. An understanding of how the brain coordinates changes in the mother's metabolism to initiate and sustain milk synthesis may help in development of interventions to prevent premature cessation of breastfeeding. Exciting new data from our lab suggest that the master clock which governs circadian rhythms coordinates the metabolic and hormonal changes needed to initiate lactation in the mother. Using transcriptome analysis, others showed that 7% of genes expressed in the breast of lactating women had circadian patterns including core clock and metabolic genes. Further, offspring of homozygous female Clock mutant mice, which have a genetic mutation that disrupts circadian rhythms, fail to thrive in a manner that suggested dam's milk production was not adequate enough to nourish their young. These findings suggest that the circadian clock in the mammary gland controls a unique set of genes important for its major function, lactation, and the master clock in the suprachiasmatic nuclei (SCN) controls other genes important to coordination of peripheral clocks and energy balance. We hypothesize that at the onset of lactation the master clock resets peripheral clocks and hormonal levels to coordinate the metabolic changes needed to initiate and sustain milk synthesis. The objective of this project is to determine 1) if changes in circadian clocks occur at the onset of lactation and 2) the effect of disrupting circadian rhythms on lactation. Our long- term goal is to determine how the brain coordinates the metabolic changes needed to initiate and sustain lactation so that strategies can be developed to increase successful breastfeeding among all women. At the completion of this study we expect to know if master and peripheral mammary/liver clocks are reset at the onset of lactation and if this resetting is associated with changes in clock output including hormones and metabolic enzymes. These findings may impact strategies geared toward increasing successful breastfeeding of infants, and provide insight into how metabolic processes are coordinated throughout the mother during changes in physiological states. PUBLIC HEALTH RELEVANCE: National targets were set in Healthy People 2010 to have at least 75% of mothers initiate breastfeeding and at least 50% of mothers exclusively breastfeed their infants for 6 months, because breast-feeding infants is associated with numerous health benefits for both mother and infant. The target for mothers initiating breast feeding is nearly met, however the target set for exclusive breast feeding for 6 months is far from being reached. Human lactation is a complex phenomena and the duration of breastfeeding is influenced by many demographic, physical, social, and psychological variables;a greater understanding of how the brain coordinates the physiological changes that occur to initiate milk synthesis may help in developing interventions and therapies aimed at increasing duration of breastfeeding.